Low-Dose Ketamine Case Studies: Clinical Outcomes and Lessons

Introduction

Clinical case studies provide a valuable complement to randomized controlled trial data by illustrating the complexities of real-world ketamine therapy -- the heterogeneity of patient presentations, the nuances of dosing decisions, and the practical challenges that arise during treatment. While case studies cannot establish causation and are inherently subject to selection bias, they offer clinically actionable insights into patient management strategies that controlled trials rarely capture.

The following five anonymized cases are composites drawn from published clinical literature and reflect common clinical scenarios encountered in low-dose ketamine practice. Patient details have been modified to protect confidentiality. Each case illustrates specific clinical principles relevant to prescribers managing ketamine therapy.

Case 1: Treatment-Resistant Depression with Partial SSRI Response

Presentation

A 47-year-old woman presented with a 12-year history of major depressive disorder (MDD). She had undergone adequate trials of four SSRI/SNRI medications (sertraline, fluoxetine, venlafaxine, duloxetine), augmentation with aripiprazole and lithium, and 12 sessions of cognitive behavioral therapy. Her current regimen was duloxetine 120 mg daily, which she described as "taking the edge off" but leaving her with persistent anhedonia, fatigue, and passive suicidal ideation without plan or intent. Baseline PHQ-9 score was 19 (moderately severe depression). MADRS score was 28.

Medical history was notable for well-controlled hypertension on lisinopril 20 mg and mild obesity (BMI 32). Screening bloodwork including hepatic function panel and complete blood count was unremarkable.

Treatment Course

The clinician initiated IV ketamine infusions at 0.5 mg/kg over 40 minutes, administered twice weekly for three weeks (six infusions). Duloxetine was continued without modification. Pre-treatment blood pressure was 138/86 mmHg; during infusions, systolic blood pressure peaked at 155-162 mmHg, returning to baseline within 30 minutes post-infusion.

By the third infusion, the patient reported improved sleep quality and a subjective "lightening" of mood. PHQ-9 at the midpoint (after infusion 3) was 14, representing a 26% reduction. Following the sixth infusion, PHQ-9 was 8 (mild depression) and MADRS was 12, representing response (greater than 50% MADRS reduction).

Maintenance and Outcome

The patient was transitioned to maintenance infusions at 0.5 mg/kg every two weeks. After eight weeks of maintenance, the interval was extended to every three weeks. At six-month follow-up, PHQ-9 remained between 6 and 9. Suicidal ideation had resolved. When one infusion was delayed by three weeks due to scheduling conflicts, PHQ-9 rose to 13, returning to 7 after resumption of treatment.

Clinical Lessons

This case illustrates the typical response trajectory for TRD patients: partial response emerging by the second or third infusion, with maximal acute-phase improvement by the end of the standard six-infusion induction. The relapse during the extended infusion gap underscores that for many patients, ketamine provides symptomatic improvement that is dependent on continued treatment rather than a durable remission from a single induction course. Blood pressure elevations remained manageable but required monitoring given the patient's hypertensive baseline.

Case 2: PTSD with Comorbid Chronic Pain

Presentation

A 34-year-old male military veteran presented with combat-related PTSD (PCL-5 score: 58) and comorbid chronic low back pain (numeric rating scale [NRS] 7/10) attributed to lumbar disc herniation sustained during service. He had failed trials of sertraline (maximum dose 200 mg), prazosin (for nightmares), and prolonged exposure therapy, which he discontinued after four sessions due to severe distress. Current medications included gabapentin 1800 mg daily and as-needed naproxen. He denied active suicidal ideation but reported significant functional impairment, social isolation, and hypervigilance.

Treatment Course

Given the dual indications of PTSD and chronic pain, the clinician initiated IV ketamine at 0.5 mg/kg over 40 minutes, with plans for six infusions over three weeks. During the first infusion, the patient experienced moderate dissociation (Clinician-Administered Dissociative States Scale [CADSS] score: 14) and reported the experience as "uncomfortable but manageable." The clinician maintained the dose for the second infusion.

By infusion three, the patient reported a notable reduction in hypervigilance and improved sleep. Pain scores had decreased to NRS 4/10. PCL-5 at the midpoint was 42 (28% reduction). After all six infusions, PCL-5 was 31 (47% reduction, meeting response criteria) and pain NRS was 3/10.

Maintenance and Outcome

The patient was transitioned to sublingual ketamine troches at 100 mg three times weekly, taken at home under a structured protocol with vital sign self-monitoring and weekly telehealth check-ins. After two months on sublingual maintenance, PCL-5 stabilized at 28-33, and pain scores remained at 2-4/10. Gabapentin was reduced to 1200 mg daily.

The patient subsequently re-engaged with trauma-focused psychotherapy, reporting that ketamine had reduced the emotional intensity of trauma memories sufficiently to tolerate exposure-based work.

Clinical Lessons

This case demonstrates ketamine's dual utility in patients with comorbid psychiatric and pain conditions -- a common presentation in clinical practice. The transition from IV induction to sublingual maintenance illustrates a practical treatment model. The patient's subsequent ability to engage in previously intolerable psychotherapy highlights an underappreciated benefit of ketamine: its potential to facilitate engagement with evidence-based psychotherapeutic interventions by reducing symptom severity.

Case 3: Chronic Neuropathic Pain Refractory to Standard Analgesics

Presentation

A 62-year-old woman with complex regional pain syndrome (CRPS) Type I affecting the right upper extremity, duration 4 years, presented for ketamine evaluation after failing physical therapy, nerve blocks (stellate ganglion, multiple courses), gabapentin (maximum tolerated dose 2400 mg due to sedation), duloxetine 60 mg, and topical lidocaine. Pain NRS averaged 8/10, with allodynia preventing use of the affected hand. She reported significant depressive symptoms secondary to pain-related disability (PHQ-9: 15) but had no prior psychiatric history.

Treatment Course

The clinician administered a series of four prolonged IV ketamine infusions at doses escalating from 0.3 mg/kg/hr to 0.5 mg/kg/hr over four-hour sessions, administered on consecutive days. This higher-dose, longer-duration protocol reflected published CRPS-specific infusion protocols. Continuous cardiac monitoring, pulse oximetry, and nursing observation were maintained throughout.

During infusions, the patient experienced dose-dependent dissociation and vivid visual imagery, managed with a calm environment and verbal reassurance. Blood pressure elevations were modest (peak systolic increase of 18 mmHg above baseline). Nausea was managed with ondansetron 4 mg IV.

At the conclusion of the four-day infusion series, pain NRS was 4/10 and allodynia had significantly improved. The patient was able to tolerate light touch on the affected extremity for the first time in two years.

Maintenance and Outcome

The patient received booster infusions at four-week intervals for three months, then every six weeks. Pain scores stabilized at NRS 3-5/10. PHQ-9 decreased to 7 without antidepressant medication, consistent with improvement in pain-driven depressive symptoms. She resumed modified occupational therapy and regained partial hand function.

At twelve-month follow-up, the patient continued to require periodic infusions (approximately every 6-8 weeks) to maintain analgesic benefit. Attempts to extend the interval beyond 10 weeks resulted in pain recurrence.

Clinical Lessons

CRPS and neuropathic pain conditions often require higher-dose and longer-duration ketamine infusion protocols compared to psychiatric indications. This case illustrates the distinction between sub-anesthetic psychiatric dosing (typically 0.5 mg/kg over 40 minutes) and the more intensive protocols used for refractory pain. The comorbid depression improvement -- without separate antidepressant treatment -- demonstrates ketamine's analgesic and antidepressant mechanisms operating in parallel. The ongoing need for maintenance infusions is typical for CRPS patients.

Case 4: Bipolar II Depression with Benzodiazepine Use

Presentation

A 39-year-old man with Bipolar II disorder presented with a current depressive episode of five months' duration. He was maintained on lamotrigine 200 mg daily (mood stabilizer) and clonazepam 1 mg twice daily for comorbid generalized anxiety disorder. Previous depressive episodes had responded to quetiapine augmentation, but the current episode had not improved after eight weeks of quetiapine 300 mg. He denied manic or hypomanic symptoms. MADRS score was 32 (severe depression). No history of psychosis.

Treatment Course

The clinician discussed concerns regarding potential benzodiazepine attenuation of ketamine response. A collaborative decision was made to gradually reduce clonazepam to 0.5 mg twice daily over two weeks prior to initiating ketamine, with close anxiety monitoring. Complete discontinuation was not attempted due to risk of benzodiazepine withdrawal.

IV ketamine was initiated at 0.5 mg/kg over 40 minutes, twice weekly. After the second infusion, MADRS had decreased to 26 (19% reduction). The response was considered suboptimal at the midpoint, and the dose was increased to 0.75 mg/kg for infusions four through six. After six infusions, MADRS was 18 (44% reduction) -- approaching but not meeting the 50% response threshold.

Given the partial response, two additional infusions were administered at 0.75 mg/kg. After eight total infusions, MADRS was 14 (56% reduction, meeting response criteria).

Maintenance and Outcome

The patient was transitioned to sublingual ketamine 150 mg twice weekly. Close mood monitoring was maintained due to the theoretical risk of ketamine-induced mood destabilization in bipolar disorder. Over four months of maintenance, no hypomanic or manic episodes occurred. MADRS remained between 12 and 17. Lamotrigine was continued as the primary mood stabilizer.

Clinical Lessons

This case highlights two important clinical considerations. First, benzodiazepine co-administration may attenuate ketamine's antidepressant response, supporting dose reduction when clinically feasible -- though abrupt discontinuation must be avoided. The slower-than-expected response trajectory may have been partially attributable to residual benzodiazepine effects. Second, bipolar depression patients require careful monitoring for mood destabilization, but the available evidence suggests that low-dose ketamine does not reliably trigger mania, particularly in patients maintained on mood stabilizers.

Case 5: Acute Suicidal Ideation in a Young Adult

Presentation

A 23-year-old woman was referred for urgent ketamine evaluation following presentation to a crisis stabilization unit with acute suicidal ideation and a formulated plan. She had a two-year history of MDD, a previous suicide attempt (medication overdose), and had been discharged from an inpatient psychiatric unit three weeks prior. Current medications were escitalopram 20 mg and mirtazapine 30 mg (initiated during hospitalization). PHQ-9 was 24 (severe depression). Columbia Suicide Severity Rating Scale (C-SSRS) indicated active ideation with specific plan.

Treatment Course

Given the acuity of suicidal ideation, the clinician initiated IV ketamine at 0.5 mg/kg over 40 minutes under close observation with a safety protocol including continuous one-to-one monitoring during and for two hours following infusion. Three infusions were administered over five days (days 1, 3, and 5).

Within four hours of the first infusion, the patient reported a meaningful reduction in the intensity of suicidal thoughts -- describing them as "still there but quieter." By 24 hours, C-SSRS indicated passive ideation without plan. After the third infusion, suicidal ideation had resolved. PHQ-9 was 14 (41% reduction from baseline).

Maintenance and Outcome

The rapid antisuicidal response was consistent with the published literature on ketamine's effects on suicidal ideation. The patient continued with three additional infusions over the following two weeks (total of six infusions) and was transitioned to sublingual maintenance while her oral antidepressant regimen was optimized. Escitalopram was switched to vortioxetine 20 mg, and the patient engaged in dialectical behavior therapy (DBT).

At three-month follow-up, suicidal ideation had not recurred. PHQ-9 was 9. The sublingual ketamine was gradually tapered and discontinued after the DBT skills and vortioxetine regimen were well established.

Clinical Lessons

Ketamine's rapid antisuicidal properties represent one of its most clinically significant advantages over conventional antidepressants. This case illustrates the "bridge" concept -- using ketamine to rapidly reduce suicide risk while slower-acting interventions (medication optimization, psychotherapy) take effect. The successful taper and discontinuation after three months demonstrates that not all patients require indefinite maintenance, particularly when the underlying treatment regimen is optimized and psychotherapeutic engagement is strong.

Overarching Clinical Themes

Several themes emerge across these cases that are relevant to prescribers:

Individualized dosing matters. Response trajectories varied substantially between patients. The TRD patient responded well at standard dosing; the bipolar patient required dose escalation; the CRPS patient needed a fundamentally different dosing paradigm. Rigid protocol adherence without clinical judgment is insufficient.

Concurrent medications influence outcomes. Benzodiazepines, mood stabilizers, and existing antidepressants all interact with ketamine's therapeutic mechanisms. A thorough medication review and, where appropriate, strategic adjustments before initiating ketamine therapy can optimize outcomes.

Maintenance is typically required. Four of five cases required ongoing ketamine administration to sustain clinical gains. Clinicians and patients should discuss the likely need for maintenance treatment during the informed consent process.

Systematic outcome measurement drives clinical decisions. In each case, validated scales (PHQ-9, MADRS, PCL-5, NRS, C-SSRS) provided objective data that informed dosing adjustments, frequency changes, and continuation decisions. Subjective clinical impression alone is insufficient for managing ketamine therapy.

Ketamine facilitates other treatments. In cases 2 and 5, ketamine's symptom reduction enabled patients to engage with psychotherapy and medication optimization that might otherwise have been impossible -- functioning as a catalyst for broader recovery.

References

• Murrough JW, et al. Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial. Am J Psychiatry. 2013;170(10):1134-1142 — Pivotal RCT establishing ketamine efficacy in TRD
• Feder A, et al. Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2014;71(6):681-688 — RCT demonstrating ketamine efficacy for PTSD
• Sigtermans MJ, et al. Ketamine Produces Effective and Long-term Pain Relief in Patients with Complex Regional Pain Syndrome Type 1. Pain. 2009;145(3):304-311 — Ketamine infusion for CRPS
• Grunebaum MF, et al. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression. Am J Psychiatry. 2018;175(4):327-335 — Ketamine's antisuicidal effects
• Frye MA, et al. Current Landscape, Unmet Needs, and Future Directions for Treatment of Bipolar Depression. J Affect Disord. 2015;169 Suppl 1:S24-S33 — Bipolar depression treatment challenges
• Andrewes HE, et al. Impact of Benzodiazepines on Ketamine Antidepressant Response. J Clin Psychopharmacol. 2023 — Evidence regarding benzodiazepine-ketamine interaction
• National Institute of Mental Health: Rapid-Acting Treatments for Treatment-Resistant Depression — NIMH research overview